U.S. patent number 7,074,840 [Application Number 10/914,378] was granted by the patent office on 2006-07-11 for light adjustable lenses capable of post-fabrication power modification via multi-photon processes.
This patent grant is currently assigned to Calhoun Vision. Invention is credited to Axel Brait, Shiao H. Chang, Robert H. Grubbs, Julia A. Kornfield.
United States Patent |
7,074,840 |
Chang , et al. |
July 11, 2006 |
Light adjustable lenses capable of post-fabrication power
modification via multi-photon processes
Abstract
The invention relates to novel photoinitiators and their use in
light adjustable compositions. The initiatives comprise two or more
multiphoton chromophores linked by a bridging compound. The
bridging compound consists of a material that is compatible with
the base material of the light adjustable composition. The novel
photoinitiator permit the readjustment of light adjustable material
without the need for significant amounts of photoabsorbers.
Inventors: |
Chang; Shiao H. (Pasadena,
CA), Grubbs; Robert H. (South Pasadena, CA), Kornfield;
Julia A. (Pasadena, CA), Brait; Axel (Pasadena, CA) |
Assignee: |
Calhoun Vision (Pasadena,
CA)
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Family
ID: |
34135282 |
Appl.
No.: |
10/914,378 |
Filed: |
August 9, 2004 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20050027031 A1 |
Feb 3, 2005 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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10324540 |
Dec 19, 2002 |
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60493746 |
Aug 8, 2003 |
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Current U.S.
Class: |
522/65; 522/172;
522/63; 522/904; 522/173; 359/234; 252/600 |
Current CPC
Class: |
C08F
2/50 (20130101); C08F 290/00 (20130101); A61F
2/1659 (20130101); C08F 290/148 (20130101); G02C
7/04 (20130101); C08L 83/04 (20130101); C08F
293/005 (20130101); A61L 27/14 (20130101); A61L
27/18 (20130101); C08G 77/045 (20130101); C08L
53/00 (20130101); A61L 27/18 (20130101); C08L
83/04 (20130101); C08L 53/00 (20130101); C08L
2666/02 (20130101); A61F 2/1635 (20130101); G03C
1/733 (20130101); C08G 77/24 (20130101); Y10S
522/904 (20130101); A61F 2/1627 (20130101); C08G
77/14 (20130101); G02C 2202/14 (20130101) |
Current International
Class: |
G03C
1/73 (20060101); C08F 2/50 (20060101); C08L
33/04 (20060101) |
Field of
Search: |
;522/65,63,172,173,904,116,117,121,153,136,137,142 ;252/600 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Primary Examiner: Berman; Susan
Attorney, Agent or Firm: Fulbright & Jaworski LLP
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATIONS
This Application claims the benefit of the priority date of U.S.
application Ser. No. 60/493,746 filed Aug. 8, 2003 and is also a
continuation in part of U.S. application Ser. No. 10/324,540 filed
Dec. 19, 2002.
Claims
What is claimed is:
1. A photoinitiator having the formula: A-B-A.sup.1 wherein A and
A.sup.1 are independently selected from multiphoton chromophores
having the formula D-.pi.-D wherein D is a tertiary amino electron
donor and .pi. is a conjugated bridge and B is a bridging compound
comprising an acrylic or siloxane moiety.
2. The photoinitiator of claim 1 wherein B comprises a siloxane
moiety having the formula: ##STR00012## wherein m and n are
integers from 1 to 10 and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are
independently selected from the group consisting of hydrogen,
alkyl, halogenated alkyl, phenyl and aryl.
3. The photoinitiator of claim 1 wherein B comprises an acrylic
moiety having the formula: ##STR00013## wherein n is an integer
ranging from 1 to 10 and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are
independently selected from the group consisting of hydrogen,
alkyl, substituted alkyl, phenyl and aryl.
4. A photoinitiator having the formula: ##STR00014## wherein m is
an integer from 1 to 10 and R.sup.1, R.sup.2, R.sup.3 and R.sup.4
independently selected from the group consisting of hydrogen,
alkyl, halogenated alkyl, phenyl and aryl.
5. A light adjustable composition comprising: a base material;
photopolymerizable macromers; a photoinitiator, said photoinitiator
having the formula: A-B-A.sup.1 wherein A and A.sup.1 are
independently selected from multiphoton chromophores and B is a
bridging compound comprising an acrylic or siloxane moiety.
6. The composition of claim 5 wherein the bridging compound is a
acrylic moiety having the general formula: ##STR00015## wherein n
is an integer from 1 to 10 and R.sup.1, R.sup.2, R.sup.3 and
R.sup.4 are independently selected from the group consisting of
hydrogen, alkyl, substituted alkyl, phenyl and aryl.
7. The composition of claim 5 wherein the bridging compound
comprises an siloxane moiety having the formula: ##STR00016##
wherein m and n are integers and R.sup.1, R.sup.2, R.sup.3 and
R.sup.4 are independently selected from the group consisting of
hydrogen, alkyl, substituted alkyl, phenyl and aryl.
8. The composition of claim 5 wherein the base material comprises
polysiloxane.
9. The composition of claim 5 wherein the base material comprises
poly(acrylate).
10. The composition of claim 5 wherein the photoinitiator has the
formula: ##STR00017## wherein m is an integer from 1 to 10, and
R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently selected from
the group consisting of hydrogen, alkyl, substituted alkyl, phenyl
and aryl.
11. The composition of claim 5 wherein the chromophores have the
formula: D.pi.-D wherein D is a teritary amino electron donor and
.pi. is a conjugated bridge.
Description
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable.
REFERENCE TO A COMPACT DISK APPENDIX
Not applicable.
TECHNICAL FIELD
The invention relates to novel photoinitiator compositions and
their use in light adjustable compositions. These novel initiators
permit the adjustment of light adjustable compositions using
visible light and provide a material that is compatible with the
base material and provides optical clarity.
BACKGROUND OF THE INVENTION
Approximately two million cataract surgery procedures are performed
in the United States annually. The procedure generally involves
making an incision in the anterior lens capsule to remove the
cataractous crystalline lens and implanting an intraocular lens in
its place. The power of the implanted lens is selected (based upon
pre-operative measurements of ocular length and corneal curvature)
to enable the patient to see without additional corrective measures
(e.g., glasses or contact lenses). Unfortunately, due to errors in
measurement, and/or variable lens positioning and wound healing,
about half of all patients undergoing this procedure will not enjoy
optimal vision without correction after surgery. Brandser et al.,
Acta Ophthalmol Scand 75:162 165 (1997); Oshika et al., J Cataract
Refract Surg 24:509 514 (1998). Because the power of prior art
intraocular lenses generally cannot be adjusted once they have been
implanted, the patient typically must choose between replacing the
implanted lens with another lens of a different power or be
resigned to the use of additional corrective lenses such as glasses
or contact lenses. Since the benefits typically do not outweigh the
risks of the former, it is almost never done.
One solution to this problem has been the development of light
adjustable intraocular lenses such as those disclosed in U.S. Pat.
No. 6,450,642. The lenses described therein are formed from a
polymer matrix having photopolymerizable macromers dispersed
therein. The photopolymerization of the macromers induces changes
in one or more properties of the lens including changes in the
optical properties. The lenses, however, require that the macromers
be fully consumed in a "lock-in" step preventing unintentional
changes in the lens by exposure to UV or ambient light. This
exhaustion of the macromers prevents further adjustments to the
lens after the initial series of corrections.
A potential method for eliminating the need for a lock-in step is
through the use of two photon initiators such as those described
and disclosed in U.S. Pat. Nos. 6,267,913; 6,316,153; 6,402,037;
6,555,682; and 6,566,529 as well as published U.S. applications
2002/0185634 and 2003/0052311. The chromophores described in these
applications require the use of high intensity light to trigger a
release of energy sufficient to initiate a polymerization reaction.
While these materials can be used, they are generally not
compatible with the materials used to make light adjustable lenses
such as siloxanes or acrylates. This incompatibility reduces the
optical clarity of the materials and can result in the leaching of
the initiators from the lens. This makes these initiators
unacceptable for use in optical elements especially contact lenses
or intraocular lenses.
It is therefore desirable to provide a photoinitiator that is
triggered by light with an intensity greater than ambient light
that is compatible with the base material of the light adjustable
composition or article.
BRIEF SUMMARY OF THE INVENTION
The invention comprises a photoinitiating composition that is
compatible with the base material used to make the light adjustable
compositions or articles. The photoinitiators of the invention
comprise the general formula: A-B-A.sup.1 wherein B is a bridging
compound comprising a monomer, homopolymer or copolymer of a
similar nature to the base material of the light adjustable
composition and A and A.sup.1, which can be the same or different,
comprising multi-photon chromophores.
In one embodiment, the bridging compound comprises siloxane or
acrylate moieties depending upon the nature of the base material.
For example, in the case of an intraocular lens made from
polysiloxanes, B is preferably also a siloxane and when the lens is
a polyacrylate, then B is an acrylate.
In one embodiment, the chromophore absorbs light via two-photon
absorption in the range of 400 1500 nm, preferably 400 to 800 nm,
most preferred 500 to 700 nm. Owning to the nature of the
chromophores, the light must be at an intensity in excess of that
encountered from ambient light and at a high enough intensity to
enable the simultaneous absorption of two or more photons during
irradiation.
The novel photoinitiators of the present invention are particularly
useful as the photoinitiator for light adjustable optical elements.
Because the photoinitiators are triggered by visible light at
intensities significantly greater than ambient light (e.g. normal
sunlight), use of these novel photoinitiators permits the
manufacture and implementation of light adjustable optical elements
which do not require a lock-in-step to prevent unwanted changes in
the optical element and can be readjusted one or more times over
the life of the optical element.
The foregoing has outlined rather broadly the features and
technical advantages of the present invention in order that the
detailed description of the invention that follows may be better
understood. Additional features and advantages of the invention
will be described hereinafter which form the subject of the claims
of the invention. It should be appreciated that the conception and
specific embodiment disclosed may be readily utilized as a basis
for modifying or designing other structures for carrying out the
same purposes of the present invention. It should also be realized
that such equivalent constructions do not depart from the invention
as set forth in the appended claims. The novel features which are
believed to be characteristic of the invention, both as to its
organization and method of operation, together with further objects
and advantages will be better understood from the following
description when considered in connection with the accompanying
figures. It is to be expressly understood, however, that each of
the figures is provided for the purpose of illustration and
description only and is not intended as a definition of the limits
of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The novel photoinitiators of the invention use light in the visible
light wavelengths but require an intensity of light much greater
than that encountered in ambient light. Thus they can be activated
using lasers or other light sources, which provide sufficient
intensity but do not require the use of ultraviolet light. The
presence of a bridging compound similar in composition to the base
material used to make the light adjustable article, improves
compatibility, helps ensure optical clarity and prevents leaching
of the photoinitiator to the aqueous environment of the eye. The
use of the photoinitiator, which is activated by high intensity
light, permits the fabrication of light adjustable materials whose
properties can be changed several times over a prolonged period of
time. The use of the novel photoinitiators of the invention will
also permit the fabrication of blue light absorbing light
adjustable lenses capable of filtering out blue light to protect
lipoftiscin filled RPE (retinal pigment epithelium) cells against
blue light damage.
The novel photoinitiators of the invention have the general
formula: A-B-A.sup.1 wherein A is a multiphoton chromophores and
A.sup.1 is a non-chromophore end-functionality or a multiphoton
chromophore that is the same as A or different and B is a bridging
compound comprising a monomer, homopolymer or copolymer having a
composition similar to the base material. For example, where the
base material comprises polysiloxanes, B will have the general
formula:
##STR00001## wherein m and n are integers greater than or equal to
1, preferably greater than or equal to 5 and less than or equal to
10. R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently
selected from the group consisting of hydrogen, alkyl, halogenated
alkyl, aryl, halogenated aryl and arylalkyl moieties.
Similarly, where the base material is a polyacrylate, B will have
the general formula:
##STR00002## wherein m, n, R.sup.1, R.sup.2, R.sup.3 and R.sup.4
are as defined above.
The multiphoton chromophore elements A and A.sup.1 are preferably
two photon chromophores that are capable of using visible light to
initiate a polymerization reaction via a multiphoton absorption.
Typically, these chromophores absorb light in the range of 200 1500
nm with from 400 900 nm preferred for 2-photon absorption. As used
herein, the term high intensity light means light at an intensity
greater than the intensity encountered under ambient conditions and
sufficient to trigger photopolymerization. For example, in one
embodiment, the initiator is triggered by light at about 532 nm at
a pulse duration of about 0.5 ns with a maximum pulse energy of
about 4 .mu.J. The chromophores useful in the practice of the
invention are modified to permit bonding to the bridging moiety.
This is typically done through the addition of one or more vinyl or
allyl groups on the chromophore but any reactive group which can
bond to a group on the bridging compound can be used.
When the chromophore has been modified by the addition of a vinyl
group, the chromophore is bonded to the bridging compound by a
vinyl-hydride reaction in the case of the silicone bridge and, for
example, ATRP (atom transfer radical polymerization) endcapping in
the case of an acrylate bridge. While this will generally occur at
a terminal hydride for a silicone bridge, the reaction can occur at
any available hydride. Thus the invention is not limited to
photoinitiators where the chromophore is attached at the end of the
bridging compound. Analogous the chromophore can be attached at any
place along the acrylate bridge, including at the ends of the
bridging acrylate.
One group of chromophores useful in the practice of the invention
have the general formula: D-.pi.-D wherein D is a tertiary amino
electron-donor group and .pi. is a conjugated bridge. For example,
the .pi. can be selected from the group consisting of fluorene,
diphenylpolyene, bis-(styryl)benzene, bis(phenylbutadienyl)benzene
and bis-(styryl)benzene.
One particularly useful chromophore has the general formula:
##STR00003## This chromophore is prepared by the addition of two
allyl groups to dibromofluorene followed by palladium coupling with
3-methoxydiphenyl-amine in the manner shown below:
##STR00004##
As shown in the structure above, the chromophore has two available
allyl groups. These groups can react with a hydride group on the
siloxane moiety or via ATRP endcapping with the radical end of an
acrylate moiety using techniques well known in the art to yield a
structure such as:
##STR00005##
The resulting photoinitiator is triggered by exposure to light in
the range of 400 900 nm but is not activated by light in the
intensity of ambient light.
As discussed above, the novel photoinitiators of the invention are
particularly useful in light adjustable compositions or articles
particularly light adjustable optical elements.
The light adjustable article or composition generally comprises a
base material which is generally formed from a polymer matrix and
photopolymerizable macromers which are incorporated into but not
bound to the base material. The novel photoinitiators are also
incorporated into the base material such that they can initiate the
photopolymerization of the macromers by multiphoton absorption upon
exposure to light of sufficient intensity and in the proper
wavelength. The photopolymerization of the macromers induces
changes in the properties of the composition. For example, in the
case of an optical element, the photopolymerization of the macromer
can cause changes in the refractive index of the base material. The
photopolymerization can also cause changes in the shape of the base
material. This may also affect the optical properties of the
material.
The invention also relates to optical elements whose optical
properties can be continuously modified or adjusted over its useful
life. This adjustment is accomplished in a self-contained system
that is without the addition or removal of material from the
element. The use of the novel photoinitiators of the present
invention permits the readjustment of the optical elements over
time. This also eliminates the need for a "lock-in" step to prevent
unwanted changes in the optical element due to exposure to ambient
light.
Typical optical elements within the scope of the invention include
data storage elements, including compact disks, digital video
disks; lenses, including but not limited to spectacle lenses;
contact lenses, intraocular lenses; mirrors, prisms, and the like.
In the preferred embodiment, the optical element is an intraocular
lens.
The optical element is typically prepared from a first polymer
matrix which gives shape to the element as well as many of its
physical properties such as hardness, flexibility and the like.
The optical element also contains a macromer dispersed therein.
This macromer may be a single compound or a combination of
compounds that is capable of stimulus-induced polymerization,
preferably photopolymerization.
The nature of the first polymer matrix and the macromer will vary
depending upon the end use contemplated for the optical element.
However, as a general rule, the first polymer matrix and the
macromer are selected such that the components that comprise the
macromer are capable of diffusion within the first polymer matrix.
Put another way, a loose first polymer matrix will tend to be
paired with larger macromer components and a tight first polymer
matrix will tend to be paired with smaller macromer components.
Upon exposure to an appropriate energy (e.g., heat or light), the
macromer typically forms a second polymer matrix in the exposed
region of the optical element. The presence of the second polymer
matrix changes the material characteristics of this portion of the
optical element to modulate its refraction capabilities. In
general, the formation of the second polymer matrix typically
increases the refractive index of the affected portion of the
optical element. After exposure, the macromer in the unexposed
region will migrate into the exposed region over time. The amount
of macromer migration into the exposed region is time dependent and
may be precisely controlled. If enough time is permitted, the
macromer components will re-equilibrate and redistribute throughout
optical element (i.e., the first polymer matrix, including the
exposed region). When the region is re-exposed to the energy
source, the macromer that has since migrated into the region (which
may be less than if the macromer were allowed to re-equilibrate)
polymerizes to further increase the formation of the second polymer
matrix. This process (exposure followed by an appropriate time
interval to allow for diffusion) may be repeated until the exposed
region of the optical element has reached the desired property
(e.g., power, refractive index, or shape). At this point, because
the novel photoinitiator require the use of light at an intensity
above ambient conditions, no further polymerization occurs until
the element is exposed to the specific wave length and intensity.
Thus, in the case of an intraocular lens, the lens may be exposed
to natural light and the like without further changes in the lens.
If adjustments are needed because of aging or changes in the
patient's health, for example, the lens can be adjusted by exposure
to an appropriate energy source.
The first polymer matrix is a covalently or physically linked
structure that functions as an optical element and is formed from a
first polymer matrix composition ("FPMC"). In general, the first
polymer matrix composition comprises one or more monomers that upon
polymerization will form the first polymer matrix. The first
polymer matrix composition optionally may include any number of
formulation auxiliaries that modulate the polymerization reaction
or improve any property of the optical element. Illustrative
examples of suitable FPMC monomers include acrylics, methacrylates,
phosphazenes, siloxanes, vinyls, homopolymers and copolymers
thereof. As used herein, a "monomer" refers to any unit (which may
itself either be a homopolymer or copolymer).sub.2 which may be
linked together to form a polymer containing repeating units of the
same. If the FPMC monomer is a copolymer, it may be comprised of
the same type of monomers (e.g., two different siloxanes) or it may
be comprised of different types of monomers (e.g., a siloxane and
an acrylic).
In one embodiment, the one or more monomers that form the first
polymer matrix are polymerized and cross-linked in the presence of
the macromer. In another embodiment, polymeric starting material
that forms the first polymer matrix is cross-linked in the presence
of the macromer. Under either scenario, the macromer components
must be compatible with and not appreciably interfere with the
formation of the first polymer matrix. Similarly, the formation of
the second polymer matrix should also be compatible with the
existing first polymer matrix. Put another way, the first polymer
matrix and the second polymer matrix should not phase separate and
light transmission by the optical element should be unaffected.
As described previously, the macromer may be a single component or
multiple components so long as: (i) it is compatible with the
formation of the first polymer matrix; (ii) it remains capable of
stimulus-induced polymerization after the formation of the first
polymer matrix: and (iii) it is freely diffusible within the first
polymer matrix. In preferred embodiments, the stimulus-induced
polymerization is photo-induced polymerization.
In general, there are two types of intraocular lenses ("IOLs"). The
first type of an intraocular lens replaces the eye's natural lens.
The most common reason for such a procedure is cataracts. The
second type of intraocular lens supplements the existing lens and
functions as a permanent corrective lens. This type of lens
(sometimes referred to as a phakic intraocular lens) is implanted
in the anterior or posterior chamber to correct any refractive
errors of the eye. In theory, the power for either type of
intraocular lenses required for emmetropia (i.e., perfect focus on
the retina from light at infinity) can be precisely calculated.
However, in practice, due to errors in measurement of corneal
curvature, and/or variable lens positioning and wound healing, it
is estimated that only about half of all patients undergoing IOL
implantation will enjoy the best possible vision without the need
for additional correction after surgery. Because prior art IOLs are
generally incapable of post-surgical power modification, the
remaining patients must resort to other types of vision correction
such as external lenses (e.g. glasses or contact lenses) or cornea
surgery. The need for these types of additional corrective measures
is obviated with the use of the intraocular lenses of the present
invention.
The inventive intraocular lens comprises a first polymer matrix and
a macromer dispersed therein. The first polymer matrix and the
macromer are as described above with the additional requirement
that the resulting lens be biocompatible.
Illustrative examples of a suitable first polymer matrix include:
polyacrylates such as polyalkyl acrylates and polyhydroxyalkyl
acrylates; polymethacrylates such as polymethyl methacrylate
("PMMA"), a polyhydroxyethyl methacrylate ("PHEMA"), and
polyhydroxypropyl methacrylate ("HPMA"); polyvinyls such as
polystyrene and polyvinylpyrrolidone ("NVP"); polysiloxanes such as
polydimethylsiloxane; polyphosphazenes, and copolymers of thereof.
U.S. Pat. No. 4,260,725 and patents and references cited therein
(which are all incorporated herein by reference) provide more
specific examples of suitable polymers that may be used to form the
first polymer matrix.
In preferred embodiments, the first polymer matrix generally
possesses a relatively low glass transition temperature ("T.sub.g")
such that the resulting IOL tends to exhibit fluid-like and/or
elastomeric behavior. In applications where flexibility is
important (e.g., intraocular lenses or contact lenses), the T.sub.g
will generally be less than 25.degree. C. preferably less than
20.degree. C. Where rigidity is important, the T.sub.g will be much
higher, e.g., 25.degree. C. to 50.degree. C.
The first polymer matrix is typically formed by cross-linking one
or more polymeric starting materials wherein each polymeric
starting material includes at least one cross-linkable group.
Illustrative examples of suitable cross-linkable groups include but
are not limited to hydride, acetoxy, alkoxy, amino, anhydride,
aryloxy, carboxy, enoxy, epoxy, halide, isocyano, olefinic, and
oxine. In more preferred embodiments, each polymeric starting
material includes terminal monomers (also referred to as endcaps)
:that are either the same or different from the one or more
monomers that comprise the polymeric starting material but include
at least one cross-linkable group. In other words, the terminal
monomers begin and end the polymeric starting material and include
at least one cross-linkable group as part of its structure.
Although it is not necessary for the practice of the present
invention, the mechanism for cross-linking the polymeric starting
material preferably is different than the mechanism for the
stimulus-induced polymerization of the components that comprise the
macromer. For example, if the macromer is polymerized by
photo-induced polymerization, then it is preferred that the
polymeric starting materials have cross-linkable groups that are
polymerized by any mechanism other than photo-induced
polymerization.
An especially preferred class of polymeric starting materials for
the formation of the first polymer matrix is polysiloxanes (also
known as "silicones") endcapped with a terminal monomer which
includes a cross-linkable group selected from the group of
unsaturated alkyl such as vinyl. Because silicone IOLs tend to be
flexible and foldable, generally smaller incisions may be used
during the IOL implantation procedure. An example of an especially
preferred polymeric starting material is
bis(vinyldimethylsilyl)-polydimethysiloxane (which is
polydimethylsiloxane that is endcapped with a vinyldimethylsilyl
terminal monomer).
The macromer that is used in fabricating IOLs is as described above
except that it has the additional requirement of biocompatibility.
The macromer is capable of stimulus-induced polymerization and may
be a single component or multiple components so long as: (i) it is
compatible with the formation of the first polymer matrix; (ii) it
remains capable of stimulus-induced polymerization after the
formation of the first polymer matrix; and (iii) it is freely
diffisable within the first polymer matrix. In general, the same
type of monomers that is used to form the first polymer matrix-may
be used as a component of the macromer. However, because of the
requirement that the macromer monomers must be diffusable within
the first polymer matrix, the macromer monomers generally tend to
be smaller (i.e., have lower molecular weights) than the monomers,
which form the first polymer matrix. In addition to the one or more
monomers, the macromer may include other components such as
initiators and sensitizers that facilitate the formation of the
second polymer matrix.
Because of the preference for flexible and foldable IOLs, an
especially preferred class of macromer monomers is polysiloxanes
endcapped with a terminal siloxane moiety that includes a
photopolymerizable group. An illustrative representation of such a
monomer is: X-Y-X.sup.1 wherein Y is a siloxane which may be a
monomer, a homopolymer or a copolymer formed from any number of
siloxane units, and X and X.sup.1 may be the same or different and
are each independently a terminal siloxane moiety that includes a
photopolymerizable group. Illustrative examples of Y include:
##STR00006## wherein m and n are independently each an integer and
R.sup.1, R.sup.2, R.sup.3, and R.sup.4, are independently each
hydrogen, alkyl (primary, secondary, tertiary, cyclo), aryl, or
heteroaryl. In preferred embodiments, R.sup.1, R.sup.2, R.sup.3,
and R.sup.4, is a C.sub.1 C.sub.10 alkyl or phenyl. Because
macromer monomers with a relatively high aryl content have been
found to produce larger changes in the refractive index of the
inventive lens, it is generally preferred that at least one of
R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is an aryl, particularly
phenyl. In more preferred embodiments. R.sup.1, R.sup.2, R.sup.3
are the same and are methyl, ethyl or propyl and R.sup.4 is
phenyl.
Illustrative examples of X and X.sup.1 (or X.sup.1 and X depending
on how the macromer polymer is depicted) are:
##STR00007## respectively wherein R.sup.5 and R.sup.6 are
independently each hydrogen, alkyl, aryl, or heteroaryl; and Z is a
photopolymerizable group.
In preferred embodiments R.sup.1 and R.sup.6 are independently each
a C.sub.1 and C.sub.10 alkyl or phenyl and Z is a
photopolymerizable group that includes a moiety selected from the
group consisting of acrylate, allyloxy, cinnamoyl, methacrylate,
stibenyl, and vinyl. In more preferred embodiments, R.sup.5 and
R.sup.6 is methyl, ethyl, or propyl and Z is a photopolymerizable
group that includes an acrylate or methacrylate moiety.
In especially preferred embodiments, an macromer monomer is of the
following formula:
##STR00008## wherein X and X.sup.1 are the same and R.sup.1,
R.sup.2, R.sup.3, and R.sup.4 are as defined previously.
Illustrative examples of such macromer monomers include
dimethylsiloxane-diphenylsiloxane copolymer endcapped with a vinyl
dimethylsilyl group; dimethylsiloxane-methylphenylsiloxane
copolymer endcapped with a methacryloxypropyl dimethylsilyl group;
and dimethylsiloxane endcapped with a
methacryloxypropyldimethylsilyl group. Although any suitable method
may be used, a ring-opening reaction of one or more cyclic
siloxanes in the presence of triflic acid has been found to be a
particularly efficient method of making one class of inventive
macromer monomers. Briefly, the method comprises contacting a
cyclic siloxane with a compound of the formula:
##STR00009## in the presence of triflic acid wherein R.sup.5,
R.sup.6, and Z are as defined previously. The cyclic siloxane may
be a cyclic siloxane monomer, homopolymer, or copolymer.
Alternatively, more than one cyclic siloxane may be used. For
example, a cyclic dimethylsiloxane tetramer and a cyclic
methyl-phenylsiloxane trimer are contacted with
bismethacryloxypropyltetramethyldisiloxane in the presence of
triflic acid to form a dimethyl-siloxane methyl-phenylsiloxane
copolymer that is endcapped with a
methacryloxylpropyl-dimethylsilane group, an especially preferred
macromer monomer.
Alternatively, the macromer of the invention may comprise
multifunctional acrylate based monomers having the general formula:
X-(A).sub.m-Q-(A).sub.m-X.sup.1 or
X-(A).sub.n-(A.sup.1).sub.m-Q-(A).sub.m-(A.sup.1).sub.n-X.sup.1
wherein Q is an acrylate based compound used to create the acrylate
monomer; A and A.sup.1 are the same or different and have the
general structure:
##STR00010## wherein R.sup.7 and R.sup.8 are alkly, haloalkyl,
aryl, haloaryl, and X and X.sup.1 contain moieties capable of
stimulus induced polymerization, preferably photopolymerizable
groups and N and M are integers.
In one embodiment the macromer has the general structure
##STR00011## wherein R.sup.9, R.sup.10 and R.sup.11a are
independently selected from the group consisting of alkyls,
haloalkyls, aryls, and haloaryls and n and m are integers and X and
X.sup.1 are as defined above.
A key advantage of the optical element of the present invention is
that an element property may be modified post-fabrication. In the
case of an IOL, for example, the modification may be made after
implantation within the eye. For example, any errors in the power
calculation due to imperfect corneal measurements and/or variable
lens positioning and wound healing may be modified in a post
surgical outpatient procedure. Additionally, corrections due to
physical changes in the patient over time can also be made.
In addition to the change in the element's refractive index, the
stimulus-induced formation of the second polymer matrix has been
found to affect the element's power by altering the shape of the
element in a predictable manner. For example, in one embodiment,
formation of the second polymer matrix changes the thermodynamic
equilibrium in this element. This in turn promotes the migration of
the macromer, which in turn can cause a change in the curvature of
the lens. As a result, both mechanisms may be exploited to modulate
an IOL property, such as power, after it has been implanted within
the eye. In general, the method for implementing an inventive
optical element having a first polymer matrix and a macromer
dispersed therein comprises: (a) exposing at least a portion of the
optical element to a stimulus whereby the stimulus induces the
polymerization of the macromer. This step may be skipped if the
element possesses the desired initial properties; (b) determining
that a change in optical properties is required or desired; (c)
exposing or reexposing at least a portion of the element to a
stimulus whereby the stimulus induces polymerization of the
macromer to cause a change in optical properties of the element;
(d) waiting for a period of time; (e) evaluating the performance of
the element.
After exposure to an external stimulus, the element may need to be
re-exposed to stimulus until the desired optical properties are
achieved.
In another embodiment, wherein an optical element's properties need
to be modified, a method for modifying the element comprises: (a)
exposing a first portion of the optical element to a stimulus
whereby the stimulus induces the polymerization of the macromer;
and (b) exposing a second portion of the lens to the stimulus.
The first element portion and the second element portion represent
different regions of the lens although they may overlap.
Optionally, the method may include an interval of time between the
exposures of the first element portion and the second element
portion. In addition, the method may further comprise re-exposing
the first element portion and/or the second element portion any
number of times (with or without an interval of time between
exposures) or may further comprise exposing additional portions of
the element (e.g., a third element portion, a fourth element
portion, etc.).
In general, the location of the one or more exposed portions will
vary depending on the type of refractive error being corrected. For
example, in one embodiment, the exposed portion of the IOL is the
optical zone, which is the center region of the lens (e.g., between
about 4 mm and about 5 mm in diameter). Alternatively, the one or
more exposed lens portions may be along IOL's outer rim or along a
particular meridian. In another embodiment, different regions of a
spectacle lens can be exposed to a stimulus thereby creating a
bifocal spectacle lens. In preferred embodiments, the stimulus is
light. In more preferred embodiments, the light is from a laser
source.
As noted above, those adjustments can be made during the course of
the initial adjustment or can occur weeks or years later. Thus, as
the needs of the users change over time, the optical properties can
be adjusted without the need for surgery or the like.
The readjustable properties of the optical element can also lead to
novel data storage devices. By controlling the region where the
second polymer matrix is found, it is possible to record data in
three dimensions and then add or change the data stored at a later
time.
As discussed above, the multiphoton initiators of the present
invention require the use of light at intensities above ambient to
induce or initiate the photopolymerization reaction. Thus the
reaction will generally not occur at ambient conditions. In
addition, when the intense light is stopped, the polymerization
reaction stops. Thus it is possible to photopolymerize only a
portion of the macromer present in the base material leaving a
significant amount of material available for further polymerization
at a later time. This time can be as short as a few days or hours
or as long as weeks, months or years. Thus the readjustment can be
done to fine tune the initial adjustment made or it can be a
complete change in characteristics of the material. For example, in
the case of an intraocular lens, the lens can be first adjusted
after implantation to achieve a lens with the desired optical
properties. If the patient's vision needs change due to aging or
growth, further refinements can be made months or years later. The
changes can be a shift of a fraction of a diopter to several
diopters depending on the patient's needs.
Although the present invention and its advantages have been
described in detail, it should be understood that various changes,
substitutions and alterations can be made herein without departing
from the invention as defined by the appended claims. Moreover, the
scope of the present application is not intended to be limited to
the particular embodiments of the process, machine, manufacture,
composition of matter, means, methods and steps described in the
specification. As one will readily appreciate from the disclosure,
processes, machines, manufacture, compositions of matter, means,
methods, or steps, presently existing or later to be developed that
perform substantially the same function or achieve substantially
the same result as the corresponding embodiments described herein
may be utilized. Accordingly, the appended claims are intended to
include within their scope such processes, machines, manufacture,
compositions of matter, means, methods, or steps.
The following examples are provided to further illustrate the
present invention. The specific limitations set forth in the
following examples are intended as illustrative and not
limitive.
EXAMPLE 1
A 250 mL round bottom flask was charged with 8.1 g (25 mmol) of
2,7-dibromofluorene, 0.54 g (3.3 mmol) of potassium iodide, 8.4 g
(150 mmol) of potassium hydroxide, and 30 mL of DMSO. The flask was
cooled to 0.degree. C. and from an addition funnel, 5.5 mL (64
mmol) of allyl bromide was added dropwise. The reaction was allowed
to come to room temperature overnight. Next morning, water was
added to precipitate out product. The yellow solid was filtered and
recrystallized from ethanol to yield 8.2 g (81 % yield) of the
9,9-diallyl-2, 7-dibromofluorene.
A 50 mL round bottom flask was charged with 2.6 g (6.3 mmol) of
9,9-diallyl-2, 7-dibromofluorene, 3.2 g (16 mmol) of
3-methoxydiphenylamine, 1.8 g (19 mmol) of sodium t-butoxide, 0.058
g (0.063 mmol) of tris(dibenzylideneacetone)dipalladium(0), 0.11 g
(0.19 mmol) of 1,1-bis(diphenylphosphino)ferrocene, and 60 mL of
toluene. The reaction was heated to 93.degree. C. for two days. The
solids were filtered off. The filtrate was adhered to silica and
purified to yield 0.25 g (6.0% yield) of the two-photon chromophore
(2 P).
EXAMPLE 2
A 50 mL round bottom flask was charged with 0.20 g of the
two-photon chromophore (2 P), 0.20 g of silicone
hydride-crosslinker (XL-H), and 10 mL of toluene. Two drops of
"Karsted's" catalyst was added, and the reaction was allowed to
stir at room temperature until GC analysis showed the disappearance
of the two-photon chromophore. The mixture was passed through
activated charcoal to remove the platinum catalyst and the solvent
was evaporated off to yield 0.36 g of (XL-2 P).
EXAMPLE 3
A 50 mL round bottom flask was charged with 1.0 g (1.5 mmol) of the
two-photon chromophore (2 P), 0.394 g (0.78 mmol) of 1 H, 13
H-tetradecamethylheptasiloxane (H-L.sub.7-H), and 10 mL of toluene.
Two drops of "Karsted's" catalyst was added, and the reaction was
allowed to stir at room temperature until GC analysis showed the
disappearance of the two-photon chromophore. The mixture was passed
through activated charcoal to remove the platinum catalyst and the
solvent was evaporated off to yield 1.1 g (76% yield) of (2
P-L.sub.7-2 P).
EXAMPLE 4
A 50 mL round bottom flask was charged with 0.63 g (1.0 mmol) of
the two-photon chromophore (2 P), 0.51 g (1.0 mmol) of 1 H, 13
H-tetradecamethylheptasiloxane (H-L.sub.7-H), and 10 mL of toluene.
Two drops of "Karsted's" catalyst was added, and the reaction was
allowed to stir at room temperature until GC analysis showed the
disappearance of the two-photon chromophore. The mixture was passed
through activated charcoal to remove the platinum catalyst and the
solvent was evaporated off to yield 0.76 g (67% yield) of
(H-L.sub.7-2 P).
EXAMPLE 5
A silicone film was molded by mixing the following:
3.08 g of an methacrylate endcapped silicone macromer (1000
g.mol.sup.-1), 0.22 g of the 2-photon initiator prepared in Example
3, 0.534 g of a hydride resin crosslinker (3000 5000 g.mol.sup.-1),
3.50 g of a silicone base polymer (reinforced with silicone resin,
LSR-9-part A). The components were mixed thoroughly in a glass
mixing vial with a spatula and the mixture was degassed in a
desiccator. Subsequently, 3.67 g of a silicone base polymer
(reinforced with silicone resin, LSR-9-part B) that contained a
Pt-catalyst for a total of 35 ppm was added and mixed thoroughly.
The mixture was degassed again to remove any air and the filled
into a 1.2 mm thick and 75*75 mm film mold. The film was cured at
37.degree. C. for 24 hours. The film was colorless and optical
transparent as measured by UV-Visible spectroscopy.
EXAMPLE 6
The film prepared in Example 5 was irradiated in a microscope
designed for 2-photon absorption. The light derived from a
Ti:Sapphire laser at 720 nm with a power of 630 mW was focused
through an 10.times. objective with a numerical aperture of 0.30.
This gave a 1.2 .mu.m-focused spot for initiation of the 2-photon
polymerization. A circular spot with a circumference of ca. 900
.mu.m was irradiated and resulted in a photopolymerized area of
this size as shown by the different refraction in the picture
below:
* * * * *